Synthesis of a fructose decorated PAGE-b-PEG-b-PLGA polymer with subsequent formulation of nanoparticles

Herein we present D-fructose decorated nanoparticles (NPs) based on a pharmarelevant copolymer consisting of poly(ethyleneglycol) (PEG) and poly(lactide-co-glycolide) (PLGA) with an additional allyl glycidyl ether (PAGE) block. The PAGE-b-PEG-b-PLGA polymer was synthesized via ring-opening polymerization and enables post-functionalization via the so-called thiol-ene ‘click’ reaction between thio-D-fructose units and the double bond of the PAGE units. The fructose decorated polymer as well as the control polymer mPEG-b-PLGA were fully characterized by size exclusion chromatography (SEC) and nuclear magnetic resonance spectroscopy (NMR). Subsequently, they were used for NP formulation via nanoprecipitation, whereby a co-formulation with a fluorescently labeled PLGA was performed to enable visibility of the particles. NPs with a hydrodynamic diameter of 100 nm with low PDI values (0.11 to 0.25) were obtained as confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies. The utilization of a 0.3% (w/v) partially hydrolyzed-poly(vinyl alcohol) solution in the formulation significantly improved the stability of the NPs during different purification and storage processes, such as centrifugation and freeze-drying. The NP stability was further examined in acetate buffer (pH 4.9) and PBS (pH 7.4) as well as in artificial lysosomal fluids (pH 4.5 and 7.4). The NPs showed good stability in all media for at least 48 h. Finally, the NPs were tested for their cytotoxicity in different cell lines (MDA-MB-231, HEK-293) whereby no harmful effects of the particles on the cells could be observed.